The objective of this project is to 1) evaluate the replication competence of Rev-independent nef- SIV, an SIV mutant that lacks a functional nef gene and that the rev-RRE axis replaced by reconstitutive transport element (CTE) of simian retrovirus Type D (SRV/D), and 2) its potential pathogenicity. In the first phase, 3 adult macaques were inoculated intravenously with different doses of Rev-independent nef- SIV. All 3 animals were systematically infected. Over approximately 18 months of follow-up, no disease has been noted. Subsequently, 5 neonatal rhesus macaques were inoculated wit the same virus, in order to bring out any potential pathogenicity. Our previous research has shown that neonatal macaques represent the most sensitive host animals for pathogenicity studies. All 5 infants became systematically infected. With over 1-year follow-up, no signs of disease have been noted in these animals. Genomic analysis of virus sequences recovered in adult and i nfant mac aques has revealed that the CTE element remains stable and the nef gene remained non-functional. We plan to continue the follow-up of these animals for several more months to rule out pathogenicity. FUNDING NIH / NIAID $42,064 4/01/96 - 3/31/01 PUBLICATIONS None P51RR00165-38 1/1/1998 - 12/31/1998 Yerkes Regional Primate Research Center